Fear-potentiated startle and electrically evoked startle mediated by synapses in rostrolateral midbrain.

Startle amplitudes are increased when acoustic startle responses are elicited in the presence of a stimulus that has previously been paired with shock. This "fear-potentiated" startle response appears to be mediated via the caudal ventral amygdalofugal pathway to the brainstem. Electrical stimulation of this pathway evokes unconditioned startlelike responses. Collision tests have shown that a monosynaptic connection from amygdala to midbrain mediates these responses. Collision tests here localize these synapses mediating electrically evoked startlelike responses to the rostrolateral midbrain in awake rats. To test whether rostrolateral midbrain synapses also mediate fear-potentiated startle, we lesioned cells in these sites with ibotenic acid. These lesions completely blocked fear potentiation of acoustic startle. These same lesions did not block potentiation of startle by d-amphetamine (6 mg/kg). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear potentiation of acoustic startle stimulus-evoked heart rate changes in rats.

The present study examined the extent to which heart rate changes evoked by acoustic startle stimuli are affected by the development of fear during startle testing. The phasic heart rate responses of rats elicited by a 120-dB startle stimulus were characterized by decelerations that habituated across trials and accelerations that developed across trials in a manner that paralleled the development of freezing behavior. A 92-dB stimulus evoked little freezing or tachycardia, yet evoked decelerations of similar magnitude to the 120-dB stimulus. Pharmacological blockade of autonomic activity was used to uncouple freezing from the heart rate accelerations and to show that the accelerations were not an artifact of the habituating decelerations. These results indicate that heart rate responses to nonsignal stimuli depend critically on a rat's previous experience with those stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment. the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R. N. Leaton, see record 1995-12737-001) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Footshock-induced sensitization of electrically elicited startle reflexes.

Acoustic startle is a short-latency reflex mediated by a neural circuit consisting of the ventral cochlear nucleus (VCN), ventral nucleus of the lateral lemniscus (VLL), the nucleus reticularis pontis caudalis (RPC), and the spinal cord. The present study sought to determine the point along this pathway where footshocks might ultimately alter neural transmission to affect startle response. Rats were implanted bilaterally with stimulating electrodes in either the VCN, VLL, or RPC. Startle could be elicited acoustically with a noise burst or electrically with a single-pulse stimulus to either the VCN, VLL, or RPC before and after a train of ten 0.6-mA, 500-ms shocks presented at a rate of 1 shock/s. Startle elicited acoustically or electrically in the VCN or VLL was significantly elevated following shocks. Data suggest that footshock sensitization ultimately alters transmission in the startle circuit at the RPC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned odor potentiation of startle in rats.

An odor previously paired with shock was shown to be an effective stimulus for potentiating the startle response in rats; (Experiments 1 and 2). This effect required more than 1 odor-shock pairing (Experiment 3), was relatively long lasting (Experiment 4), and was specific to the odor previously paired with shock (Experiment 5). The implications of these findings for the startle probe procedure and for neural models of learning and memory based on results obtained with that procedure are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats.

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explicitly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats

The Afa-family repetitive sequences were isolated from barley (Hordeum vulgare, 2n = 14) and cloned as pHvA14. This sequence distinguished each barely chromosome by in situ hybridization. Double color fluorescence in situ hybridization using pHvA14 and 5S rDNA or HvRT-family sequence (subtelomeric sequence of barley) allocated individual barley chromosomes showing a specific pattern of pHvA14 to chromosome 1H to 7H. As the case of the D genome chromosomes of Aegilops squarrosa and common wheat (Triticum aestivum) hybridized by its Afa-family sequences, the signals of pHvA14 in barley chromosomes tended to appear in the distal regions that do not carry many chromosome band markers. In the telomeric regions these signals always placed in more proximal portions than those of HvRT-family. Based on the distribution patterns of Afa-family sequences in the chromosomes of barley and D genome chromosomes of wheat, we discuss a possible mechanism of amplification of the repetitive sequences during the evolution of Triticeae. In addition, we show here that HvRT-family also could be used to distinguish individual barley chromosomes from the patterns of in situ hybridization.     

Peripheral and central components of alerting: Habituation of acoustic startle, orienting responses, and elicited waveforms.

Behavioral orienting (OR), the acoustic startle reflex (ASR), pontogeniculooccipital (PGO) waves in the lateral geniculate body, and midlatency auditory evoked responses (MLR) represent components of alerting. The habituation rate for each was examined to test the hypothesis that OR, ASR, and PGO waves have related underlying neural mechanisms and determine the similarity in responsiveness between elicited PGO waves (PGOE) and elicited waves in the thalamic central lateral nucleus (CLE), a site that yields MLR. PGOE and CLE waves did not habituate in amplitude after 120 tones; however, the pattern of responses for each waveform was different. OR and ASR significantly decreased amplitude across trials with OR exhibiting a faster, more pronounced decrement. Some separation exists between the peripheral (OR and ASR) and central (PGOE and CLE) components of alerting. PGO and CL waves may have common underlying neural mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitization of the acoustic startle reflex by footshock.

Administration of footshock (500-ms duration, 0.2–2.4 mA) increased the amplitude of the startle reflex for a long time after its presentation. The effect occurred with a single footshock, although its magnitude and consistency across animals were greater with 5 or 10 footshocks presented 1/s. The facilitatory effect came on within 2–4 min with a 0.6-mA shock, peaking in about 10 min and then dissipating over the next 40 min. Stronger shocks also increased startle, but with a more delayed onset of facilitation (8–20 min). Footshocks increased startle in rats not previously given startle-eliciting stimuli, indicating sensitization rather than dishabituation. The facilitatory effect may not be attributable to a rapid conditioning to the experimental context, because a change in lighting conditions from shock presentation to testing did not attenuate shock sensitization. This excitatory effect of shock on startle may represent the unconditioned effect of shock that can become associated with a neutral stimulus to support classical fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian modulation of the rat acoustic startle response.

The acoustic startle response (ASR) of male rats was measured during several sessions over a 24-hr period in both a light–dark cycle and a constant-dark condition. Each session consisted of 10 trials each at 80, 90, 100, 110, and 120 dB white noise. The results indicate robust daily and circadian modulation of ASR amplitude that consist of an approximately 2-fold nocturnal increase at eliciting-stimuli intensities above 80 dB. Similar results were observed in female rats in constant-dark conditions. To determine whether daily changes in auditory thresholds were responsible for the observed modulation, ASR reflex modification procedures were used. These procedures were designed to measure auditory thresholds at frequencies of 10 and 40 kHz at several times of day. The results suggest a lack of significant circadian differences in auditory thresholds at these frequencies. This study demonstrates a novel role of the rat circadian system in the modulation of ASR amplitude. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural systems involved in fear and anxiety measured with fear-potentiated startle.

A good deal is now known about the neural circuitry involved in how conditioned fear can augment a simple reflex (fear-potentiated startle). This involves visual or auditory as well as shock pathways that project via the thalamus and perirhinal or insular cortex to the basolateral amygdala (BLA). The BLA projects to the central (CeA) and medial (MeA) nuclei of the amygdala, which project indirectly to a particular part of the acoustic startle pathway in the brainstem. N-methyl-D-aspartate (NMDA) receptors, as well as various intracellular cascades in the amygdala, are critical for fear learning, which is then mediated by glutamate acting in the CeA. Less predictable stimuli, such as a long-duration bright light or a fearful context, activate the BLA, which projects to the bed nucleus of the stria terminalis (BNST), which projects to the startle pathway much as the CeA does. The anxiogenic peptide corticotropin-releasing hormone increases startle by acting directly in the BNST. CeA-mediated behaviors may represent stimulus-specific fear, whereas BNST-mediated behaviors are more akin to anxiety. NMDA receptors are also involved in extinction of conditioned fear, and both extinction in rats and exposure-based psychotherapy in humans are facilitated by an NMDA-partial agonist called D-cycloserine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contingency awareness and fear inhibition in a human fear-potentiated startle paradigm.

Fear-potentiated startle is defined as an increase in the magnitude of the startle reflex in the presence of a stimulus that was previously paired with an aversive event. It has been proposed that a subject's awareness of the contingencies in the experiment may affect fear-potentiated startle. The authors adapted a conditional discrimination procedure (AX+/BX-), previously validated in animals, to a human fear-potentiated startle paradigm in 50 healthy volunteers. This paradigm allows for an assessment of fear-potentiated startle during threat conditions as well as inhibition of fear-potentiated startle during safety conditions. A response keypad was used to assess contingency awareness on a trial-by-trial basis. Both aware and unaware subjects showed fear-potentiated startle. However, awareness was related to stimulus discrimination and fear inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Circadian modulation in the rat acoustic startle circuit.

The acoustic startle reflex (ASR) in rats exhibits robust circadian modulation, with ASR amplitudes greater during subjective night. To identify the location of this modulation, startle reactions were evoked either acoustically or electrically via electrodes implanted in the primary ASR circuit. Startle amplitudes were compared at different times in the circadian cycle. In constant environmental conditions, startle amplitudes were greater in subjective night for acoustically evolved and for electrically evoked reactions from the ventral lateral lemniscus and medial longitudinal fasciculus. The results show that at least 1 site of circadian modulation must occur at some point in the circuit after the last brainstem synapse in the caudal pontine reticular formation, at the level of spinal interneurons or motoneurons or at the neuromuscular junction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdala kindling-resistant (SLOW) or -prone (FAST) rat strains show differential fear responses

The authors compared two rat strains, selectively bred for their susceptibility to amygdala kindling, with respect to their performance on various behavioral and learning tasks that are associated with fear and anxiety. The two rat strains differed significantly in measurements of exploration of novel and familiar environments, as well as in reactivity to footshock and fear-based learning. The kindling-resistant (SLOW) strain exhibited a lower ratio of open- to closed-arm entries in the elevated plus-maze, less activity over days in the open field, greater behavioral suppression in the open-field if previously footshocked, greater freezing in the inhibitory avoidance task, and slower acquisition and poorer retention in the one-way avoidance task than did the kindling-prone (FAST) strain. These experiments suggest that the SLOW rats are more expressively fearful than the FAST rats, particularly with respect to environmentally triggered freezing or immobility. Further, these observations imply that the relatively constrained excitability of the amygdala network in the SLOW rats might mediate their relatively greater expression of fear and anxiety compared with the FAST rats.     

Refractory period and habituation of acoustic startle response in rats.

Conducted 4 experiments, each with 10 male albino rats, to determine the time course of the refractory period of the acoustic startle response. The refractory effect was shown to be highly dependent upon the interval between 2 startle stimuli but independent of the intensity of the stimuli at a given interval, provided that the intensity of both stimuli was the same. A model based on summation of refractory effects to repetitive stimulation did not predict habituation to repetitive stimulation. The interaction between refractory effect and habituation was discussed, and it was suggested that short interstimulus intervals reduce the effective intensity of the habituation stimulus so that the effects of frequency and intensity become confounded in habituation studies where the interval between habituation stimuli invades the refractory period of the response being studied. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacological and anatomical analysis of fear conditioning using the fear-potentiated startle paradigm.

Pharmacological and anatomical analyses of fear conditioning using the fear-potentiated startle paradigm are reviewed. This test measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with a shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety because it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Fear-potentiated startle is selectively decreased by drugs such as diazepam, morphine, and buspirone that reduce fear or anxiety clinically. By combining behavioral, anatomical, physiological, and pharmacological approaches, it should soon be possible to determine each neural pathway that is required for a stimulus signaling fear to alter startle behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways so as to affect behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ontogeny of fear-potentiated startle: Effects of earlier-acquired fear memories.

Research has shown that learned fear emerges in a response-specific sequence. For example, freezing is observed at a younger age than is potentiated startle (P. Hunt & B. A. Campbell, 1997). The present study shows that the age at which a specific learned fear response emerges is influenced by the animal's early experiences. Specifically, fear potentiation of startle emerges earlier in development if the rat is given prior fear conditioning to a different stimulus. Some constraints of this "facilitation" effect are determined in follow-up experiments. This facilitation effect may provide a novel way of testing the development of the neural circuits underlying learned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early behaviorism and verbal mediating responses.

Largely overlooked are many "earlier behavioristic or stimulus-response analyses of increasingly complex behavioral phenomena in part by means of concepts and principles involving mediating responses and stimuli… primarily but not exclusively, verbal mediating responses and stimuli… . Meyer, Watson, Hunter, Dashiell, Kantor, and others clearly anticipated the essential features of many more recent analyses." Watson's ideas and those of his contemporaries are discussed. Hull is regarded as "the transition" between the earlier and more recent concepts concerning verbal mediating responses. From Psyc Abstracts 36:02:2AD85G. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Startle amplitude and fear in an acoustic startle paradigm: Lesions to the brachium of the inferior colliculus or the lateral tegmental tract.

In 2 Experiments, startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in an acoustic startle response (ASR) paradigm in rats. Lesions to lateral tegmental tract (LTG), a pathway medial to brachium of the inferior colllciulus (BIC), significantly decreased freezing and produced a persistent 5-fold increase in ASR amplitude compared with sham-operated controls. Lesions to BIC increased both ASR amplitude (2-fold) and freezing. Neither BIC not LTG lesions affected startle amplitude when startle was elicited by a brief footshock stimulus. Characteristics of the lesion effects were tested with manipulations of interstimulus interval, stimulus intensity, and prepulse inhibition. The data suggest (a) an ascending pathway medial to BIC that carries the fear-inducing dimensions of an acoustic stimulus and (b) a descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry. (PsycINFO Database Record (c) 2010 APA, all rights reserved)